The leading view as to etiology of peptic ulcer is that it is induced by imbalance of the aggressive factor such as hydrochloric acid or pepsin and the defensive factor such as mucosal resistance. Type 2 histamine (H.sub.2) receptor antagonists such as cimetidine which has widely been used for the treatment of peptic ulcer depress the aggressive factor and thereby shows high healing effect on peptic ulcer, but on the other hand, these agents cause decrease of gastric mucosal resistance when administered continuously, and it is assumed that it is one of the reasons of recurrence of ulcer. Accordingly, it is very desirable to develop an antiulcer drug having properties well balanced in both of depression of the aggressive factor and increase of the defensive factor. Besides, in the aged patients, there is comparatively frequently observed the peptic ulcer with low gastric acidity, and hence, it is also desired to develop a drug having an activity of specifically increasing the defensive factor.
By the way, there are known some 2-(1-piperazinyl)-4-phenylquinoline derivatives which have some pharmacological activities. These are summarized below.
It is disclosed in U.S. Pat. No. 4,237,135 that 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline and salts thereof have an antireserpine activity, inhibitory effect on spontaneous locomotor activity, and the like and are useful as an antidepressant with neuroleptic-like properties such as inhibition of central nervous system and further that the compounds have also antitremorine activity.
It is disclosed in U.S. Pat. Nos. 3,542,785 and 3,668,207 that 2-amino-4-arylquinoline derivatives including 6-chloro-2-(4-methyl-1-piperazinyl)-4-phenylquinoline have antiinflammatory and diuretic activities.
It is disclosed in Chem. Pharm. Bull., 28, 2618 (1980) that the pharmacological activities of the compounds as disclosed in the above U.S. Pat. Nos. 4,237,135, 3,542,785 and 3,668,207 and related compounds were evaluated from the viewpoint of screening antidepressant having also neuroleptic-like properties such as inhibition of central nervous system. Besides, it is also reported that some of these compounds have antitremorine activity.
The present inventors have studied as to pharmacological activities of 2-(1-piperazinyl)-4-phenylquinoline derivatives, and in the studies, they have found that the compounds having a specific substituent on the phenyl ring at the 4-position have cytoprotective effect and are useful as an antiulcer agent and a therapeutic agent for inflammatory gastrointestinal diseases, and then, the present invention has been accomplished.